title: The effect of etomidate on adrenal function in critical illness: a systematic review.
abstract: OBJECTIVE
  Although etomidate is a preferred anesthetic agent for rapid sequence intubation (RSI) in critical illness, as an inhibitor of cortisol synthesis (11β-hydroxylase), it may be associated with adrenal dysfunction. The objectives are to review the effects of etomidate versus comparator anesthetics in critical illness for: primary outcome of mortality and secondary outcome of adrenal insufficiency (AI).
  
  
  METHODS
  Studies were extracted using MEDLINE and SCOPUS, regardless of language, between 1983 and 2010 using the keywords etomidate, intensive care units (ICU), critical illness, intensive care, glucocorticoids, and adrenal insufficiency. Studies of single dose etomidate versus comparator anesthetics with outcomes of adrenal function and/or mortality were included. All reviewers performed electronic data searches. One reviewer extracted data, which were checked by the other reviewers. Authors of trials were contacted for supplemental data. Primary outcome was 28-day mortality. AI was defined per article.
  
  
  RESULTS
  Two hundred sixty-three articles were screened, and 21 articles (19 independent data sets) were evaluated. Meta-analysis comparing etomidate versus non-etomidate anesthesia demonstrated an increased risk ratio (RR) for AI of 1.64 (range 1.52-1.77; 14 studies, 2,854 patients, P<0.0001, I(2)=88%) and an increased RR for mortality of 1.19 (1.10-1.30; 14 studies, 3,516 patients, P<0.0001, I(2)=64%). Significance of re-analysis for mortality within the subset of sepsis was maintained [RR 1.22 (1.11-1.35), 7 studies, n=1,767, I(2)=74%, P<0.0001], but not for trials without sepsis [RR=1.15 (0.97-1.35), 7 studies, n=1,749, I(2)=53%, P=0.10].
  
  
  CONCLUSIONS
  There is an increased rate of AI and mortality in critically ill patients who received etomidate.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Saint Louis University School of Medicine, 1402 South Grand Blvd, St. Louis, MO 63104, USA. albertsg@slu.edu
authors.forename: Stewart G
authors.initials: SG
authors.lastname: Albert
authors.forename: Srividya
authors.initials: S
authors.lastname: Ariyan
authors.forename: Ayesha
authors.initials: A
authors.lastname: Rather
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects*; D000309:Adrenal Insufficiency / Q000139:chemically induced*; D016638:Critical Illness; D005045:Etomidate / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology* / Q000627:therapeutic use; D007362:Intensive Care Units
chemical_list: D006993:Hypnotics and Sedatives; D005045:Etomidate